Adenoviruses having modified fiber proteins

- Genetic Therapy, Inc.

An adenovirus wherein the adenovirus fiber protein includes a ligand which is specific for a receptor located on a desired cell type. The adenovirus may have at least a portion of the adenovirus fiber protein removed and replaced with a ligand which is specific for a receptor located on a desired cell type, or the adenovirus may include a fusion protein of the adenovirus fiber protein and the ligand. Such an adenovirus may also include a gene(s) encoding a therapeutic agent(s) and may be "targeted" in order to deliver such gene(s) to a desired cell type.

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Claims

1. A method of expressing a therapeutic agent in an animal, comprising:

administering to an animal an adenovirus wherein the adenovirus fiber includes a ligand which is specific for a receptor located on a desired cell type, and wherein said adenovirus includes at least one DNA sequence encoding a therapeutic agent.

2. The method of claim 1 wherein said adenovirus is administered in an amount of from 1 plaque forming unit to about 10.sup.14 plaque forming units.

3. The method of claim 2 wherein said adenovirus is administered in an amount of from about 10.sup.6 plaque forming units to about 10.sup.13 plaque forming units.

4. The method of claim 1 wherein at least a portion of the adenovirus fiber protein is removed and replaced with a ligand which is specific for a receptor located on a desired cell type.

5. The method of claim 1 wherein said adenovirus includes a fusion protein of an adenovirus fiber protein and a ligand which is specific for a receptor located on a desired cell type.

6. A method of expressing a therapeutic agent in a eukaryotic cell, comprising:

transducing a eukaryotic cell with an adenovirus wherein the adenovirus fiber includes a ligand which is specific for a receptor located on a desired cell type, and wherein said adenovirus includes at least one DNA sequence encoding a therapeutic agent.

7. An adenovirus wherein at least a portion of the adenovirus fiber protein is removed and replaced with a ligand which is a member of the TNF superfamily of ligands.

8. The adenovirus of claim 7 wherein said ligand is lymphotoxin-.alpha..

9. The adenovirus of claim 7 wherein said ligand is lymphotoxin-.beta..

10. The adenovirus of claim 7 wherein said ligand is Fas ligand.

11. The adenovirus of claim 7 wherein said ligand is CD 27.

12. The adenovirus of claim 7 wherein said ligand is OX-40.

13. The adenovirus of claim 7 wherein said ligand is a CD30 ligand.

14. The adenovirus of claim 13 wherein said adenovirus further includes DNA encoding a negative selective marker.

Referenced Cited
U.S. Patent Documents
5559099 September 24, 1996 Wickham et al.
Foreign Patent Documents
WO 94/10323 May 1994 WOX
Other references
  • Bisbee, Genetic Engineering News 17(8):1 et seq (1997). B.N. Fields et al., eds. Fundamental Virology, 2nd ed. New York: Raven Pres, 1991, p. 779. "Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy," Orkin and Motulsky, Co-chairs, Dec. 7, 1995. Levine et al., (1993) Am. J. Dis. Child 147(11):1167-1174. Jolly, (1994) Cancer Gene Therapy 1(1):51-64.
Patent History
Patent number: 5756086
Type: Grant
Filed: Feb 6, 1996
Date of Patent: May 26, 1998
Assignee: Genetic Therapy, Inc. (Gaithersburg, MD)
Inventors: Alan McClelland (Gaithersburg, MD), Susan C. Stevenson (Frederick, MD)
Primary Examiner: Johnny F. Railey, II
Attorneys: Elliot M. Olstein, Raymond J. Lillie
Application Number: 8/591,492
Classifications
Current U.S. Class: 424/932; 435/691; 435/1723; 435/3201; 536/234; 536/2372
International Classification: C12N 1586; C12N 1562; C12N 1534; A61K 4800;